P1043: OUTCOME OF PATIENTS WITH PREFIBROTIC MYELOFIBROSIS FROM A LARGE ACADEMIC CENTER
Authors: L. Masarova, P. Bose, N. Pemmaraju, H. Chifotides, L. Zhou, Z. Estrov, H. Kantarjian, S. Verstovsek
Journal: HemaSphere (2022)

Background: The 2016 WHO classification includes prefibrotic primary myelofibrosis (pre-PMF; fibrosis grading 0-1) and overt PMF (fibrosis grading 2–3). Pre-PMF has favorable survival when compared to overt PMF, however pre-PMF patients with intermediate -2 or high risks IPSS still have poor outcome (Guglielmelli et al. Blood. 2017;129(24):3227–3236). Aims: We aimed to characterize pre-PMF patients referred to our institution between the years of 2000-2020. We specifically investigated the role of known IPSS prognostic factors separated into i) clinical factors (CF): presence of either hemoglobin [hgb] < 10 g/dL / white cells [WBC] > 25 x109/L] or peripheral blasts [bl] ≥1%]; ii) age > 65 years and iii) systemic symptoms (IPSS defined; Cervantes, et al. Blood. 2009;113(13):2895–901). Methods: This retrospective study included 130 patients with newly diagnosed pre-PMF (median 1.5 months from diagnosis to presentation) and available bone marrow fibrosis grading (Thiele, J. et al. Haematologica. 2005. 90, 1128–1132). Demographics were expressed by descriptive statistics. Overall survival was estimated from the time of presentation using Kaplan Meier method with log rank test. Results: Clinical characteristics are detailed in Table 1, PART I. Fibrosis degree included grade 0 in 9, grade 0/1 in 7 and grade 1 in 114 patients, respectively. IPSS risks were as follows: low (N 22), intermediate 1 (N 50), intermediate 2 (N 30) and high (N 28). Thirty-five patients had no i-iii) factors (27%), symptoms only were in 49 patients (38%), one CF without and with symptoms was noticed in 9 (7%) and 22 (17%) patients, respectively, and 15 (11%) patients had 2 CF +/- symptoms. Median OS of the entire cohort was 68 months (95% CI 42-94) with 54% of patients being alive at 5 years. Overall survival (95% CI) per IPSS scores: low-intermediate 1 and 2 - high were not reached, 179 months (65-not expressed), 65 months (32-98) and 27 months (5-49), respectively. Median OS (95% CI) of patients without i-iii) factors (age < 65 years, no symptoms and no CF) and patients with only symptoms (all ages included) was not reached; median OS of patients with one CF with and without symptoms was of 48 months (33-63) and 47 months (37-57), respectively and median OS of patients with 2 CF +/- symptoms was of 16 months (8-24). Detailed separation of survivals per age categories and IPSS subgroups is provided in Table 1, PART II. Over the median follow-up of 43 months (95% CI 28-59), 7 patients progressed to acute leukemia with time to progression of 40 months (95% CI 9-178). Forty-one percent of patients (n = 53) required MF therapy during their follow-up, including 35 patients with JAK inhibitors and 8 with stem cell transplantation, respectively. Patients without the need for therapy or those who received JAK inhibitor had median OS of 81 (95% CI 65-not estimated) and 100 months (95% CI 17-183), respectively. This was superior to treated patients without exposure to JAK inhibitors (median OS of 45 months, 95% CI 16-47). Image:Summary/Conclusion: Presence of more adverse clinical factors is the strongest predictor of unfavorable outcome of patients with pre-PMF. Use of JAK inhibitors might have significantly improved the outcome of patients with constitutional symptoms.